Polycythemia is a common response to hypoxia, but its adaptive value is doubtful because the advantages of increased O2 carrying capacity are usually exceeded by an associated depression of cardiac output. However, most studies have been done in normoxia and ignore the possibility that hypoxia, the natural habitat of secondary polycythemia, could have vasodilator effects which might minimize depression of cardiac output. Also, the mechanism of cardiac output depression in polycythemia is unclear and may not represent a direct consequence of increased blood viscosity. Evidence is presented that the decreased cardiac output in polycythemia may instead represent the activity of baro-reflexes aimed at maintenance of constant blood pressure with increasing hematocrit. Blood pressure may receive a higher homeostatic priority than oxygen transport. Lastly, polycythemia may lead to severe hypoxemia through ventilatory depression. While mild hypoxia is a ventilatory stimulant, severe hypoxia results in ventilatory depression. Polycythemia has been shown to reduce cerebral blood flow and could increase central nervous system hypoxia during hypoxemia. This could lead to ventilatory depression and worsened hypoxemia. These tissues will be examined in anesthetized dogs before and after elevation of hematocrit by isovolume exchange transfusion of whole blood (out) for packed red cells (in). We intend to determine the extent to which hypoxic vasodilation negates or possibly reverses the decrement of oxygen transport with polycythemia. Second, we will test the hypothesis that baro-reflexes aimed at maintenance of a constant systemic arterial blood pressure are responsible for the depression of cardiac output and oxygen transport in polycythemia. Third, we will determine whether polycythemia limits the increase in cerebral blood flow which normally preserves cerebral oxygen delivery during hypoxia and whether this leads to hypoxic ventilatory depression. The findings should be of great value in understanding a fundamental response to hypoxia and should be helpful in making therapeutic decisions in polycythemic patients.